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Blood, 15 January 2008, Vol. 111, No. 2, pp. 776-784.
Prepublished online as a Blood First Edition Paper on September 21, 2007; DOI 10.1182/blood-2007-05-088310.
Previous Article | Next Article 
Submitted May 2, 2007
Accepted September 13, 2007
Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high resolution single nucleotide polymorphism oligonucleotide genomic microarray
Norihiko Kawamata*, Seishi Ogawa, Martin Zimmermann, Motohiro Kato, Masashi Sanada, Kari Hemminki, Go Yamatomo, Yasuhito Nannya, Rolf Koehler, Thomas Flohr, Carl W Miller, Jochen Harbott, Wolf-Dieter Ludwig, Martin Stanulla, Martin Schrappe, Claus R Bartram, and H Phillip Koeffler
Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA, United States
Regeneration Medicine of Hematopoiesis, University of Tokyo, School of Medicine, Tokyo, Japan
Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School (MHH), Hannover, Germany
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany
Department of Pediatric Hematology and Oncology, Justus Liebig University, Gießen, Germany
Department of Hematology, Oncology and Tumor Immunology, Robert-Rossle-Clinic at the HELIOS-Clinic Berlin-Buch, Charite, Berlin, Germany
Department of Pediatrics, University of Kiel, Kiel, Germany
* Corresponding author; email: kawamatan{at}cshs.org.
Pediatric acute lymphoblastic leukemia (ALL) is a malignant disease resulting from accumulation of genetic alterations. A robust technology, single nucleotide polymorphism oligonucleotide genomic microarray (SNP-chip) in concert with bioinformatics offers the opportunity to discover the genetic lesions associated with ALL. We examined 399 pediatric ALL samples and their matched remissiom marrows at 50,000/ 250,000 SNP sites using a SNP-chip platform. Correlations between genetic abnormalities and clinical features were examined. Three common genetic alterations were found: deletion of ETV6, deletion of p16INK4A and hyperdiploidy, as well as, a number of novel recurrent genetic alterations. Uniparental disomy (UPD) was a frequent event, especially affecting chromosome 9. A cohort of children with hyperdiploid ALL without gain of chromosomes 17 and 18 had a poor prognosis. Molecular allelokaryotyping is a robust tool to define small genetic abnormalities including UPD which is usually overlooked by standard methods. This technique was able to detect subgroups with a poor prognosis based on their genetic status.

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